Efficacy and Safety of Bleselumab in Preventing the Recurrence of Primary Focal Segmental Glomerulosclerosis in Kidney Transplant Recipients: A Phase 2a, Randomized, Multicenter Study.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease and frequently recurs after kidney transplantation. Recurrent FSGS (rFSGS) is associated with poor allograft and patient outcomes. Bleselumab, a fully human immunoglobulin G4 anti-CD40 antagonistic monoclonal antibody, disrupts CD40-related processes in FSGS, potentially preventing rFSGS. METHODS: A phase 2a, randomized, multicenter, open-label study of adult recipients (aged ≥18 y) of a living or deceased donor kidney transplant with a history of biopsy-proven primary FSGS. The study assessed the efficacy of bleselumab combined with tacrolimus and corticosteroids as maintenance immunosuppression in the prevention of rFSGS >12 mo posttransplantation, versus standard of care (SOC) comprising tacrolimus, mycophenolate mofetil, and corticosteroids. All patients received basiliximab induction. The primary endpoint was rFSGS, defined as proteinuria (protein-creatinine ratio ≥3.0 g/g) with death, graft loss, or loss to follow-up imputed as rFSGS, through 3 mo posttransplant. RESULTS: Sixty-three patients were followed for 12 mo posttransplantation. Relative decrease in rFSGS occurrence through 3 mo with bleselumab versus SOC was 40.7% (95% confidence interval, -89.8 to 26.8; P = 0.37; absolute decrease 12.7% [95% confidence interval, -34.5 to 9.0]). Central-blinded biopsy review found relative (absolute) decreases in rFSGS of 10.9% (3.9%), 17.0% (6.2%), and 20.5% (7.5%) at 3, 6, and 12 mo posttransplant, respectively; these differences were not statistically significant. Adverse events were similar for both treatments. No deaths occurred during the study. CONCLUSIONS: In at-risk kidney transplant recipients, bleselumab numerically reduced proteinuria occurrence versus SOC, but no notable difference in occurrence of biopsy-proven rFSGS was observed.

Bilateral Renal Auto-Transplantation for Retroperitoneal Sarcomas: Is It Underutilized?

Sarcomas are a rare tumor of mesenchymal origin. The liposarcoma is the most common sarcoma of the retroperitoneum. Liposarcomas are typically low grade, and present at an advanced stage and a large size. We report a case of a large retroperitoneal liposarcoma, approximately 50 kg, encasing both kidneys, which was managed via a two-stage resection and staged renal auto-transplantation into the intra-peritoneal pelvis. The patient maintained normal renal function throughout, and remains disease free two years post-resection. Renal auto-transplantation with pelvic placement may facilitate improved margin-free resection. Renal relocation may allow the use of curative-intent ablative therapies such as radiofrequency ablation and radiation in cases of retroperitoneal recurrence.

Vasopressin for Post-kidney Transplant Hypotension.

Introduction: Hypotension after deceased donor kidney transplant (DDKT) is a risk factor for delayed graft function (DGF) and poor graft survival (GS). We hypothesize that vasopressin use in hypotensive DDKT recipients (DDKTRs) to increase blood pressure (BP) reduces DGF rates and is safe without increasing mortality. Methods: Group with vasopressin "study group" (n = 45) was defined as DDKTRs between 2012 and 2017 who required vasopressin for hypotension systolic BP (SBP) <120 mm Hg or diastolic BP (DBP) <60 mm Hg. DDKTRs with no-vasopressin "comparison group" (n = 90) were propensity score-matched DDKTRs between 2012 and 2017 without vasopressin use. Primary outcomes were GS, creatinine and allograft biopsy rate at 1 year, DGF rate, and death during transplant hospitalization. Results: Vasopressin group had lower mean maximum and minimum SBP and DBP in the operating room (OR). Median vasopressin start time post-DDKT was 2 hours (interquartile range [IQR] 1-6), and duration of use was 42 hours (IQR 24-63). DGF, creatinine at 1 year, and allograft biopsy rates were comparable. No deaths occurred during transplant hospitalization. Multivariable analysis did not find an effect of vasopressin use on GS. Conclusion: Treatment of hypotensive DDKTRs with vasopressin is safe and facilitated similar graft function and survival with that of nonhypotensive patients. In the absence of a randomized control trial, our study supports the safety of vasopressin therapy to prevent the adverse effects of hypotension.

The effect of temperature on physical activity: an aggregated timeseries analysis of smartphone users in five major Chinese cities.

BACKGROUND: Physical activity is an important factor in premature mortality reduction, non-communicable disease prevention, and well-being protection. Climate change will alter temperatures globally, with impacts already found on mortality and morbidity. While uncomfortable temperature is often perceived as a barrier to physical activity, the actual impact of temperature on physical activity has been less well studied, particularly in China. This study examined the associations between temperature and objectively measured physical activity among adult populations in five major Chinese cities. METHODS: Aggregated anonymized step count data was obtained between December 2017-2018 for five major Chinese cities: Beijing, Shanghai, Chongqing, Shenzhen, and Hong Kong. The associations of temperature with daily aggregated mean step count were assessed using Generalized Additive Models (GAMs), adjusted for meteorological, air pollution, and time-related variables. RESULTS: Significant decreases in step counts during periods of high temperatures were found for cold or temperate climate cities (Beijing, Shanghai, and Chongqing), with maximum physical activity occurring between 16 and 19.3 °C. High temperatures were associated with decreases of 800-1500 daily steps compared to optimal temperatures. For cities in subtropical climates (Shenzhen and Hong Kong), non-significant declines were found with high temperatures. Overall, females and the elderly demonstrated lower optimal temperatures for physical activity and larger decreases of step count in warmer temperatures. CONCLUSIONS: As minor reductions in physical activity could consequentially affect health, an increased awareness of temperature's impact on physical activity is necessary. City-wide adaptations and physical activity interventions should seek ways to sustain physical activity levels in the face of shifting temperatures from climate change.

Individual socioeconomic status as a modifier of the association between high ambient temperature and hospital admissions: a time series study in Hong Kong, 2010-2019.

Few studies have examined individual socioeconomic status (SES) as a potential modifier of ambient temperature-health associations, especially for temperature-related hospitalizations. We fit penalized distributed lag non-linear models within generalized additive models to study the short-term associations (0-3 days) between temperature and hospital admissions stratified by common causes, age, and individual SES, as determined by whether patients received public assistance (PA) to cover their medical fee at the time of hospitalizations, during the hot season (May 15 to October 15) in Hong Kong for the years 2010-2019. We calculated the ratio of relative risk (RRR) and corresponding 95% confidence interval (CI) to statistically test the difference of the associations between PA groups. For 75 + patients, the PA group had significantly increased risks of hospitalizations at higher temperature for most causes, with relative risks (RR, 99th %ile vs. 25%ile) and 95% CIs of 1.138 (1.099, 1.179), 1.057 (1.008, 1.109), and 1.163 (1.094, 1.236) estimated for all non-cancer non-external, circulatory, and respiratory admissions, respectively. There were slight decreases of RRs with higher temperature for 75 + patients without PA. The strengths of temperature-hospitalization associations were strongly and significantly different between PA groups for all examined causes for 75 + patients, with the most considerable discrepancy found for ischemic heart disease (RRR = 1.266; 95% CI, 1.137, 1.410). Hospitalizations for patients aged 15-74 were less affected by heat, and the difference of the associations between groups was small. Individual SES is a significant modifier of high temperature-hospitalization associations in Hong Kong among the elderly. Public health interventions are needed to better protect this subpopulation from adverse health impacts of high temperature.

Return to work after injury in Hong Kong: prospective multi-center cohort study.

PURPOSE: Trauma remains a major cause of morbidity and disability worldwide; however, reliable data on the health status of an urban Asian population after injury are scarce. The aim was to evaluate 1-year post-trauma return to work (RTW) status in Hong Kong. METHODS: This was a prospective, multi-center cohort study involving four regional trauma centers from 2017 to 2019 in Hong Kong. Participants included adult patients entered into the trauma registry who were working or seeking employment at the time of injury. The primary outcome was the RTW status up to 1 year. The Extended Glasgow Outcome Scale, 12-item Short Form (SF-12) survey and EQ5D were also obtained during 1-, 3-, 6-, 9-, and 12-month follow-ups. Multivariable Cox proportional hazards regression analysis was used for analysis. RESULTS: Six hundred and seven of the 1115 (54%) recruited patients had RTW during the first year after injury. Lower physical requirements (p = 0.003, HR 1.51) in pre-injury job nature, higher educational levels (p < 0.001, HR 1.95), non-work-related injuries (p < 0.001, HR 1.85), shorter hospital length of stay (p = 0.007, HR 0.98), no requirement for surgery (p = 0.006, HR 1.34), and patients who could be discharged home (p = 0.006, HR 1.43) were associated with RTW within 12 months post-injury. In addition, 1-month outcomes including extended Glasgow Outcome Scale ≥ 6 (p = 0.001, HR 7.34), higher mean SF-12 physical component summary (p = 0.002, HR 1.02) and mental component summary (p < 0.001, HR 1.03), and higher EQ5D health index (p = 0.018, HR 2.14) were strongly associated with RTW. CONCLUSIONS: We have identified factors associated with failure to RTW during the first year following in Hong Kong including socioeconomic factors, injury factors and treatment-related factors and 1-month outcomes. Future studies should focus on the interventions that can impact on RTW outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03219424.

Procedure: Laparoscopic Donor Nephrectomy.

Minimally invasive approaches for laparoscopic donor nephrectomy are necessary to limit surgical morbidity, and technical challenges differ from those encountered during other laparoscopic renal surgeries. Presented here is a step-by-step guide for laparoscopic donor nephrectomy-focusing on pure laparoscopic and hand-assisted techniques. Both straight laparoscopic and hand-assisted nephrectomies were performed in healthy donors who met transplantation criteria in terms of global health and psychologic well-being. Patient positioning, trocar placement, surgical steps, incision closure, and postoperative care are reviewed. Standard equipment used to complete this procedure is itemized. This guide outlines indications, preoperative preparation, and procedural steps for laparoscopic donor nephrectomy. The techniques and the evolution thereof represent our experience since 2002 for 510 cases. The attached videos demonstrate a high-volume surgeon's typical approach while factoring in anatomical variation. In both cases, the donor nephrectomies were without incident and the patient's postoperative courses were without complication. A basic framework for donor nephrectomy is presented highlighting surgical steps we believe to be essential for graft preservation and ultimately effective transplantation. Although no two cases are the same, systematic approaches will allow for timely case completion, fewer complications, and better donor/recipient outcomes.

Combined liver-kidney transplantation with positive crossmatch: Role of delayed kidney transplantation.

BACKGROUND: Positive crossmatch (XM+) combined liver-kidney transplantation due to preformed donor-specific human leukocyte antigen antibodies has produced mixed results. We sought to understand the role of delayed kidney transplant approach in XM+ combined liver-kidney transplantations. METHODS: XM+ combined liver-kidney transplantations were retrospectively reviewed. T- and B-cell XM, complement-dependent cytotoxic crossmatch, and flow cytometric crossmatch were performed prospectively. RESULTS: Of 183 combined liver-kidney transplantations performed (2002-2019), 114 (62%) were with "delayed" kidney transplant approach and 19 (19 of 183, 10%) were XM+. Of 19 XM+ combined liver-kidney transplantations, kidney transplant was "delayed" in 14 by an average of 47 hours (range 24-64 hours) from liver transplant. There was a significant reduction in both class I (mean pre-liver transplant mean fluorescence intensity (MFI) 26,230 versus mean post-liver transplant and pre-delayed kidney transplant MFI 3,272, P = .01) and total MFI (mean pre-liver transplant MFI 27,233 vs mean post liver transplant and predelayed kidney transplant MFI 11,469, P = .01). However, there was no significant change in the MFI of class II donor-specific antibodies (mean pre-liver transplant MFI 17,899 versus post-liver transplant and pre-delayed kidney transplant MFI 14,341, P = .19). None of XM+ delayed kidney transplants had delayed graft function, and there was no antibody-mediated rejection. One-year patient survival for the XM+ combined liver-kidney transplantation with delayed kidney transplant approach was 92.9%, which is comparable to patient survival of XM- combined liver-kidney transplantation. Whereas patient survival in recipients before "delayed" approach ("simultaneous"; n = 5) was 40% when liver-kidney transplants were performed simultaneously (P = .06). CONCLUSION: In sensitized combined liver-kidney transplantation recipients, the "delayed" kidney transplant approach is associated with a significant reduction in total and class I donor-specific antibodies after liver transplant before kidney transplant, enabling therapeutic interventions such as plasmapheresis, if needed, providing optimal outcomes similar to crossmatch recipients.

A National Survey of Practice Patterns for Accepting Living Kidney Donors With Prior COVID-19.

INTRODUCTION: A critical question facing transplant programs is whether, when, and how to safely accept living kidney donors (LKDs) who have recovered from COVID-19 infection. The purpose of the study is to understand current practices related to accepting these LKDs. METHODS: We surveyed US transplant programs from 3 September through 3 November 2020. Center level and participant level responses were analyzed. RESULTS: A total of 174 respondents from 115 unique centers responded, representing 59% of US LKD programs and 72.4% of 2019 and 72.5% of 2020 LKD volume (Organ Procurement and Transplantation Network-OPTN 2021). In all, 48.6% of responding centers had received inquiries from such LKDs, whereas 44.3% were currently evaluating. A total of 98 donors were in the evaluation phase, whereas 27.8% centers had approved 42 such donors to proceed with donation. A total of 50.8% of participants preferred to wait >3 months, and 91% would wait at least 1 month from onset of infection to LD surgery. The most common reason to exclude LDs was evidence of COVID-19-related AKI (59.8%) even if resolved, followed by COVID-19-related pneumonia (28.7%) and hospitalization (21.3%). The most common concern in accepting such donors was kidney health postdonation (59.2%), followed by risk of transmission to the recipient (55.7%), donor perioperative pulmonary risk (41.4%), and donor pulmonary risk in the future (29.9%). CONCLUSION: Practice patterns for acceptance of COVID-19-recovered LKDs showed considerable variability. Ongoing research and consensus building are needed to guide optimal practices to ensure safety of accepting such donors. Long-term close follow-up of such donors is warranted.

Pre-diagnosis and early post-diagnosis dietary soy isoflavone intake and survival outcomes: A prospective cohort study of early stage breast cancer survivors.

BACKGROUND: There is concern that the estrogen-like effects of soy isoflavones may stimulate mammary tumor growth and interfere with the efficacy of breast cancer treatment. This study aimed to examine prospectively the associations of dietary soy isoflavone intake with all-cause mortality and breast cancer (BC) specific mortality and recurrence among BC survivors. DESIGN: The study included 1460 Chinese women with early-stage incident BC. Pre-diagnosis and early post-diagnosis soy food intakes were assessed at study entry, and at 18-month follow-up using validated soy food frequency questionnaire. Associations of soy isoflavone intake with prognostic outcomes within 48 months were examined using multivariable adjusted Cox proportional hazards models. RESULTS: We observed increasing pre-diagnosis and early post-diagnosis soy isoflavone intakes up to the third quartile (Q3) were associated with reductions for adverse prognostic outcomes. Relative to the lowest quartile (Q1), the hazard ratios (HRs) for all-cause mortality for pre-diagnosis and post-diagnosis Q3 intake were respectively 0.34 (95% CI, 0.16-0.74), and 0.44 (95% CI, 0.22-0.89). A similar risk reduction was observed for pre- and post-diagnosis intakes and BC-specific mortality when comparing Q3 versus Q1 with the respective HRs 0.36 (95% CI, 0.16-0.82), and 0.49 (95% CI, 0.23-1.01). Subgroup analyses showed more favourable prognostic outcomes in association with moderate soy intake among premenopausal women, those with triple negative cancer and recipients of tamoxifen treatment. CONCLUSION: Moderate soy isoflavone intake was associated with favourable prognostic outcomes in Chinese early stage BC survivors.

Living Donor Gifted Lithiasis: Long-Term Outcomes in Recipients.

OBJECTIVES: Presence of nephrolithiasis in a living donor has been at least a relative contraindication to living donor nephrectomy. The concern for stone recurrence and outcomes has been one of the reasons for reluctance to consider these medically complex donors. We evaluate long-term outcomes in recipients of kidney grafts from donors with nephrolithiasis, or history of nephrolithiasis, and provide results from our experience at Indiana University. MATERIALS AND METHODS: We retrospectively reviewed 57 donor-recipient pairs, where the allograft was received from a living donor with symptomatic calculi, or with imaging evidence of kidney stones, between 2003 and 2018. This research study was done in compliance with the ethical standards set forth in the Helsinki Congress. RESULTS: The mean age of recipients was 46±19 years and 58% were male. Kidney recipients were followed for a median of 3.5 years and 59.6% of patients had follow-up imaging studies. None of the recipients had obstructing renal calculi or related infections. None of the recipients required any interventions for recurrent calculi and no stone episode lead to adverse event to the graft. Hyperoxaluria and hypercalciuria were the most common risk factors in 24-hour urine collections obtained from donors. CONCLUSIONS: Our findings from a single large center looking at kidney recipient outcomes over a long follow-up period found that gifted lithiasis is a safe procedure. Careful selection of "medically complex donors" with kidney stones based on appropriate guidelines is a key step. Further studies are needed to help develop consensus guidelines.

Association of technologically assisted integrated care with clinical outcomes in type 2 diabetes in Hong Kong using the prospective JADE Program: A retrospective cohort analysis.

BACKGROUND: Diabetes outcomes are influenced by host factors, settings, and care processes. We examined the association of data-driven integrated care assisted by information and communications technology (ICT) with clinical outcomes in type 2 diabetes in public and private healthcare settings. METHODS AND FINDINGS: The web-based Joint Asia Diabetes Evaluation (JADE) platform provides a protocol to guide data collection for issuing a personalized JADE report including risk categories (1-4, low-high), 5-year probabilities of cardiovascular-renal events, and trends and targets of 4 risk factors with tailored decision support. The JADE program is a prospective cohort study implemented in a naturalistic environment where patients underwent nurse-led structured evaluation (blood/urine/eye/feet) in public and private outpatient clinics and diabetes centers in Hong Kong. We retrospectively analyzed the data of 16,624 Han Chinese patients with type 2 diabetes who were enrolled in 2007-2015. In the public setting, the non-JADE group (n = 3,587) underwent structured evaluation for risk factors and complications only, while the JADE (n = 9,601) group received a JADE report with group empowerment by nurses. In a community-based, nurse-led, university-affiliated diabetes center (UDC), the JADE-Personalized (JADE-P) group (n = 3,436) received a JADE report, personalized empowerment, and annual telephone reminder for reevaluation and engagement. The primary composite outcome was time to the first occurrence of cardiovascular-renal diseases, all-site cancer, and/or death, based on hospitalization data censored on 30 June 2017. During 94,311 person-years of follow-up in 2007-2017, 7,779 primary events occurred. Compared with the JADE group (136.22 cases per 1,000 patient-years [95% CI 132.35-140.18]), the non-JADE group had higher (145.32 [95% CI 138.68-152.20]; P = 0.020) while the JADE-P group had lower event rates (70.94 [95% CI 67.12-74.91]; P < 0.001). The adjusted hazard ratios (aHRs) for the primary composite outcome were 1.22 (95% CI 1.15-1.30) and 0.70 (95% CI 0.66-0.75), respectively, independent of risk profiles, education levels, drug usage, self-care, and comorbidities at baseline. We reported consistent results in propensity-score-matched analyses and after accounting for loss to follow-up. Potential limitations include its nonrandomized design that precludes causal inference, residual confounding, and participation bias. CONCLUSIONS: ICT-assisted integrated care was associated with a reduction in clinical events, including death in type 2 diabetes in public and private healthcare settings.

The Mortality Risk and Socioeconomic Vulnerability Associated with High and Low Temperature in Hong Kong.

(1) Background: The adverse health effect associated with extreme temperature has been extensively reported in the current literature. Some also found that temperature effect may vary among the population with different socioeconomic status (SES), but found inconsistent results. Previous studies on the socioeconomic vulnerability of temperature effect were mainly achieved by multi-city or country analysis, but the large heterogeneity between cities may introduce additional bias to the estimation. The linkage between death registry and census in Hong Kong allows us to perform a city-wide analysis in which the study population shares virtually the same cultural, lifestyle and policy environment. This study aims to examine and compare the high and low temperature on morality in Hong Kong, a city with a subtropical climate and address a key research question of whether the extreme high and low temperature disproportionally affects population with lower SES. (2) Methods: Poisson-generalized additive models and distributed-lagged nonlinear models were used to examine the association between daily mortality and daily mean temperature between 2007-2015 with other meteorological and confounding factors controlled. Death registry was linked with small area census and area-level median household income was used as the proxy for socioeconomic status. (3) Results: 362,957 deaths during the study period were included in the analysis. The minimum mortality temperature was found to be 28.9 °C (82nd percentile). With a subtropical climate, the low temperature has a stronger effect than the high temperature on non-accidental, cardiovascular, respiratory and cancer deaths in Hong Kong. The hot effect was more pronounced in the first few days, while cold effect tended to last up to three weeks. Significant heat effect was only observed in the lower SES groups, whilst the extreme low temperature was associated with significantly higher mortality risk across all SES groups. The older population were susceptible to extreme temperature, especially for cold. (4) Conclusions: This study raised the concern of cold-related health impact in the subtropical region. Compared with high temperature, low temperature may be considered a universal hazard to the entire population in Hong Kong rather than only disproportionally affecting people with lower SES. Future public health policy should reconsider the strategy at both individual and community levels to reduce temperature-related mortality.

Secular trends in all-cause and cause-specific mortality rates in people with diabetes in Hong Kong, 2001-2016: a retrospective cohort study.

AIMS/HYPOTHESIS: The aim of the study was to describe trends in all-cause and cause-specific mortality rates in Hong Kong Chinese people with diabetes from 2001 to 2016. METHODS: The Hong Kong Diabetes Surveillance Database (HKDSD) is a territory-wide diabetes cohort identified from the Hong Kong Hospital Authority electronic medical record system. Deaths between 2001 and 2016 were identified from linkage to the Hong Kong Death Registry. We used Joinpoint regression analysis to describe mortality patterns among people with diabetes by age and sex, and standardised mortality ratios (SMRs) to compare all-cause mortality rates in people with and without diabetes. RESULTS: Between 2001 and 2016, a total of 390,071 men and 380,007 women aged 20 years or older with diabetes were included in the HKDSD. There were 96,645 deaths among men and 88,437 deaths among women. Mortality rates for all-cause, cardiovascular disease and cancer among people with diabetes declined by 52.3%, 72.2% and 65.1% in men, respectively, and by 53.5%, 78.5% and 59.6% in women, respectively. Pneumonia mortality rates remained stable. The leading cause of death in people with diabetes has shifted from cardiovascular disease to pneumonia in the oldest age group, with cancer remaining the most common cause of death in people aged 45-74 years. The all-cause SMRs for men declined from 2.82 (95% CI 2.72, 2.94) to 1.50 (95% CI 1.46, 1.54), and for women, they declined from 3.28 (95% CI 3.15, 3.41) to 1.67 (95% CI 1.62, 1.72). However, among people aged 20-44 years, the declines in all-cause mortality rates over the study period were not statistically significant for both men (average annual per cent change [AAPC]: -3.2% [95% CI -7.3%, 1.0%]) and women (AAPC: -1.2% [95% CI -6.5%, 4.4%]). The SMRs in people aged 20-44 years fluctuated over time, between 7.86 (95% CI 5.74, 10.5) in men and 6.10 (95% CI 3.68, 9.45) in women in 2001, and 4.95 (95% CI 3.72, 6.45) in men and 4.92 (95% CI 3.25, 7.12) in women in 2016. CONCLUSIONS/INTERPRETATION: Absolute and relative mortality has declined overall in people with diabetes in Hong Kong, with less marked improvements in people under 45 years of age, calling for urgent action to improve care in young people with diabetes.

Progression of glucose intolerance and cardiometabolic risk factors over a decade in Chinese women with polycystic ovary syndrome: A case-control study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with increased metabolic risk, though data on long-term follow-up of cardiometabolic traits are limited. We postulated that Chinese women with PCOS would have higher risk of incident diabetes and cardiometabolic abnormalities than those without PCOS during long-term follow-up. METHODS AND FINDINGS: One hundred ninety-nine Chinese women with PCOS diagnosed by the Rotterdam criteria and with a mean age of 41.2 years (SD = 6.4) completed a follow-up evaluation after an average of 10.6 ± 1.3 years. Two hundred twenty-five women without PCOS (mean age: 54.1 ± 6.7 years) who underwent baseline and follow-up evaluation over the same period were used for comparison. Progression of glycaemic status of women both with and without PCOS was assessed by using 75-g oral glucose tolerance test (OGTT) screening with the adoption of 2009 American Diabetes Association diagnostic criteria. The frequency of impaired glucose regulation, hypertension, and hyperlipidaemia of women with PCOS at follow-up has increased from 31.7% (95% CI 25.2%-38.1%) to 47.2% (95% CI 40.3%-54.2%), 16.1% (95% CI 11.0%-21.2%) to 34.7% (95% CI 28.1%-41.3%), and 52.3% (95% CI 45.3%-59.2%) to 64.3% (95% CI 57.7%-71.0%), respectively. The cumulative incidence of diabetes mellitus (DM) in follow-up women with PCOS is 26.1% (95% CI 20.0%-32.2%), almost double that in the cohort of women without PCOS (p < 0.001). Age-standardised incidence of diabetes among women with PCOS was 22.12 per 1,000 person-years (95% CI 10.86-33.37) compared with the local female population incidence rate of 8.76 per 1,000 person-years (95% CI 8.72-8.80) and 10.09 per 1,000 person-years (95% CI 4.92-15.26, p < 0.001) for women without PCOS in our study. Incidence rate for women with PCOS aged 30-39 years was 20.56 per 1,000 person-years (95% CI 12.57-31.87), which is approximately 10-fold higher than that of the age-matched general female population in Hong Kong (1.88 per 1,000 person-years, [95% CI 1.85-1.92]). The incidence rate of type 2 DM (T2DM) of both normal-weight and overweight women with PCOS was around double that of corresponding control groups (normal weight: 8.96 [95% CI 3.92-17.72] versus 4.86 per 1,000 person-years [95% CI 2.13-9.62], p > 0.05; overweight/obese: 28.64 [95% CI 19.55-40.60] versus 14.1 per 1,000 person-years [95% CI 8.20-22.76], p < 0.05). Logistic regression analysis identified that baseline waist-to-hip ratio (odds ratio [OR] = 1.71 [95% CI 1.08-2.69], p < 0.05) and elevated triglyceride (OR = 6.63 [95% CI 1.23-35.69], p < 0.05) are associated with the progression to T2DM in PCOS. Limitations of this study include moderate sample size with limited number of incident diabetes during follow-up period and potential selection bias. CONCLUSIONS: High risk of diabetes and increased cardiovascular disease risk factors among Chinese women with PCOS are highlighted in this long-term follow-up study. Diabetes onset was, on average, 10 years earlier among women with PCOS than in women without PCOS.

Renal Autotransplant and Celiac Artery Bypass for Aneurysmal Degeneration Related to Neurofibromatosis Type 1.

We present a case of an 18-year-old female with neurofibromatosis type 1 who presented with abdominal pain and weight loss secondary to chronic mesenteric ischemia due to celiac axis occlusion and was subsequently found to have multiple visceral artery aneurysms. Of clinical significance, 2 aneurysms of the right renal artery were noted at the hilum, with the larger one having a diameter of 2.4 cm. After initial endovascular treatment with stenting of a concurrent pancreaticoduodenal artery pseudoaneurysm, staged aorto-hepatic bypass and right nephrectomy with renal autotransplantation after back table resection of the aneurysmal segments were successfully completed.

Burden of unique and low prevalence somatic mutations correlates with cancer survival.

Tumor mutational burden correlates with improved survival and immunotherapy response in some malignancies, and with tumor aggressiveness in others. To study the link between mutational burden and survival, we analyzed survival effects of tumor exonic missense mutation burden (TEMMB) across 6947 specimens spanning 31 cancers which have undergone whole exome sequencing as part of TCGA. We adjusted TEMMB for age, sex, stage, and recruitment center, and computed Cox-proportional models of TEMMB survival effects. We assigned a recurrence score (RS) to each cohort, defining RS as the burden of recurrent mutations exceeding 1% population prevalence. High TEMMB was associated with improved survival in cutaneous melanoma: hazard ratio (HR) = 0.71 [0.60-0.85], p = 0.0002, urothelial bladder carcinoma: HR = 0.74 [0.59-0.93], p = 0.01, and ovarian carcinoma: HR = 0.80 [0.70-0.93], p = 0.003. High TEMMB was associated with decreased survival in colorectal adenocarcinoma: HR = 1.32 [1.00-1.74], p < 0.05. We identified that TEMMB survival effects were governed by the balance of recurrent and non-recurrent mutations. In cancers with a low RS, high TEMMB was correlated with better survival outcomes (r = 0.49, p = 0.02). In conclusion, TEMMB effects on survival depend on recurrent mutation enrichment; tumor types that are highly enriched in passenger mutations show a survival benefit in the setting of high tumor mutational burden.

Excess Burden of Mental Illness and Hospitalization in Young-Onset Type 2 Diabetes: A Population-Based Cohort Study.

Background: Type 2 diabetes (T2D) increases hospitalization risk. Young-onset T2D (YOD) (defined as onset before age 40 years) is associated with excess morbidity and mortality, but its effect on hospitalizations is unknown. Objective: To determine hospitalization rates among persons with YOD and to examine the effect of age at onset on hospitalization risk. Design: Prospective cohort study. Setting: Hong Kong. Participants: Adults aged 20 to 75 years in population-based (2002 to 2014; n = 422 908) and registry-based (2000 to 2014; n = 20 886) T2D cohorts. Measurements: All-cause and cause-specific hospitalization rates. Negative binomial regression models estimated effect of age at onset on hospitalization rate and cumulative bed-days from onset to age 75 years for YOD. Results: Patients with YOD had the highest hospitalization rates by attained age. In the registry cohort, 36.8% of YOD bed-days before age 40 years were due to mental illness. The adjusted rate ratios showed increased hospitalization in YOD versus usual-onset T2D (onset at age ≥40 years) (all-cause, 1.8 [95% CI, 1.7 to 2.0]; renal, 6.7 [CI, 4.2 to 10.6]; diabetes, 3.7 [CI, 3.0 to 4.6]; cardiovascular, 2.1 [CI, 1.8 to 2.5]; infection, 1.7 [CI, 1.4 to 2.1]; P < 0.001 for all). Models estimated that intensified risk factor control in YOD (hemoglobin A1c level <6.2%, systolic blood pressure <120 mm Hg, low-density lipoprotein cholesterol level <2.0 mmol/L [<77.3 mg/dL], triglyceride level <1.3 mmol/L [<115.1 mg/dL], waist circumference of 85 cm [men] or 80 cm [women], and smoking cessation) was associated with a one-third reduction in cumulative bed-days from onset to age 75 years (97 to 65 bed-days). Limitation: Possible residual confounding. Conclusion: Adults with YOD have excess hospitalizations across their lifespan compared with persons with usual-onset T2D, including an unexpectedly large burden of mental illness in young adulthood. Efforts to prevent YOD and intensify cardiometabolic risk factor control while focusing on mental health are urgently needed. Primary Funding Source: Asia Diabetes Foundation.

The global epidemiology of bladder cancer: a joinpoint regression analysis of its incidence and mortality trends and projection.

We tested the hypotheses that the global incidence of bladder cancer was increasing but its mortality was reducing and its incidence was positively correlated with country-specific socioeconomic development. We retrieved data on age-standardized incidence and mortality rates/100,000 from the GLOBOCAN database in 2012. Temporal patterns were examined for 39 countries from the Cancer Incidence in Five Continents volumes I-X and other national registries. We evaluated the correlation between the incidence/mortality rates and Human Development Index (HDI)/ logarithmic values of Gross Domestic Product per capita (GDP). The average annual percent change of the incidence and mortality rates in the most recent 10 years was examined by joinpoint regression analysis. The highest incidence rates were observed in Southern Europe, Western Europe and North America. The mortality rates were the highest in Western Asia and Northern Africa. The incidence was positively correlated with HDI (r = 0.66 [men]; r = 0.50 [women]) and to a lesser extent logarithmic values of GDP per capita (r = 0.60 [men]; r = 0.50 [women], all p < 0.01). Many European countries experienced incidence rise. A substantial mortality reduction was observed in most countries, yet increases in mortality rates were observed in the Philippines and Iceland. These findings identified countries where more preventive actions are required.

Incidence and mortality of lung cancer: global trends and association with socioeconomic status.

We examined the correlation between lung cancer incidence/mortality and country-specific socioeconomic development, and evaluated its most recent global trends. We retrieved its age-standardized incidence rates from the GLOBOCAN database, and temporal patterns were assessed from global databases. We employed simple linear regression analysis to evaluate their correlations with Human Development Index (HDI) and Gross Domestic Product (GDP) per capita. The average annual percent changes (AAPC) of the trends were evaluated from join-point regression analysis. Country-specific HDI was strongly correlated with age-standardized incidence (r = 0.70) and mortality (r = 0.67), and to a lesser extent GDP (r = 0.24 to 0.55). Among men, 22 and 30 (out of 38 and 36) countries showed declining incidence and mortality trends, respectively; whilst among women, 19 and 16 countries showed increasing incidence and mortality trends, respectively. Among men, the AAPCs ranged from -2.8 to -0.6 (incidence) and -3.6 to -1.1 (mortality) in countries with declining trend, whereas among women the AAPC range was 0.4 to 8.9 (incidence) and 1 to 4.4 (mortality) in countries with increasing trend. Among women, Brazil, Spain and Cyprus had the greatest incidence increase, and all countries in Western, Southern and Eastern Europe reported increasing mortality. These findings highlighted the need for targeted preventive measures.